Brain iron deposition and movement disorders in hereditary haemochromatosis without liver failure: A cross-sectional study.

BACKGROUND AND PURPOSE: Hereditary haemochromatosis (HH) is the most common inherited disorder of systemic iron excess in Northern Europeans. Emerging evidence indicates that brain iron overload occurs in HH. Despite this observation, there is a paucity of literature regarding central neurological manifestations, in particular movement disorders, in HH. The current study documents deep gray matter (DGM) nuclei iron deposition, movement disorders, and clinicoradiological correlations in HH without liver failure. METHODS: This is a cross-sectional study. Consecutive subjects with HFE-haemochromatosis without liver disease were recruited from an outpatient gastroenterology clinic. Age- and sex-matched healthy controls (HCs) were enrolled. Iron content in individual DGM nuclei was measured as mean susceptibility on magnetic resonance imaging using quantitative susceptibility mapping-based regions of interest analysis. Occurrence and phenotype of movement disorders were documented and correlated with patterns of DGM nuclei iron deposition in subjects with HH. RESULTS: Fifty-two subjects with HH and 47 HCs were recruited. High magnetic susceptibility was demonstrated in several DGM nuclei in all HH subjects compared to HCs. Thirty-five subjects with HH had movement disorders. Magnetic susceptibility in specific DGM nuclei correlated with individual movement disorder phenotypes. Serum ferritin, phlebotomy frequency, and duration were poor predictors of brain iron deposition. CONCLUSIONS: Abnormal brain iron deposition can be demonstrated on imaging in all subjects with HH without liver failure. A significant proportion of these subjects manifest movement disorders. Peripheral iron measurements appear not to correlate with brain iron deposition. Therefore, routine neurological examination and quantitative brain iron imaging are recommended in all subjects with HH.

Palliative Care Discussions in Multiple System Atrophy: A Retrospective Review.

OBJECTIVE: Multiple system atrophy (MSA) is an incurable neurodegenerative illness in which progressive symptoms, including stridor and acute laryngeal obstruction, occur. Advanced care planning and palliative care discussions in people living with MSA are not well defined. The aim of the present study is to evaluate advanced care planning and current practices in palliative care in MSA to identify opportunities for improving quality of care. METHODS: The study is a retrospective chart review assessing the focus and timing of palliative care discussions in people living with MSA. Some 22 charts were reviewed. RESULTS: A total of 22 patients were included. The most common symptoms were parkinsonism, orthostatic hypotension, GI/GU dysfunction, ataxia and gait impairment. Six patients had stridor. Of the palliative care discussions that took place, the most common topics were diagnosis, symptoms or symptom management, and prognosis. In the majority of patients who died and who had a do-not-attempt-resuscitation order, discussions surrounding resuscitation and goals of care took place only hours before death. CONCLUSIONS: There is no standard approach to advanced care planning and palliative care discussions in people living with MSA. We propose a framework to guide advanced care planning and palliative care discussions in MSA.

Validity, Reliability, and Insights from Applying the McGill Quality of Life Questionnaire to People Living with Parkinson's Disease (MQoL-PD).

Existing quality-of-life instruments for Parkinson's disease (PD) may not fully assess quality of life (QoL) for people with PD in a holistic and multidimensional manner. This study examines the subscale structure, validity, and internal-consistency reliability of the McGill Quality of Life (MQoL) Questionnaire in a sample of people with PD. This cross-sectional study evaluates the MQoL-PD by using Cronbach's alpha and principal components analysis. A total of 81 consenting people with PD from a tertiary care outpatient clinic were studied. Scores were tabulated for the motor Unified Parkinson's Disease Rating Scale (mUPDRS), the Short Form Health Survey (SF-36), the Parkinson's Disease Questionnaire (PDQ-39), the MQoL Single-Item Scale (MQoL-SIS), and the MQoL Questionnaire (MQoL). Cronbach's alpha for the MQoL-PD was: physical symptoms, 0.83; psychological symptoms, 0.59; and existential/support symptoms, 0.76. Important contributors to QoL in PD include mobility, bowel and bladder function, fatigue, and pain. The MQoL Questionnaire is a valid and reliable measure of physical, psychological, and existential/support symptoms for people with PD.

Telehealth management in movement disorder: a retrospective study.

BACKGROUND: Management of chronic diseases such as movement disorders can be challenging. Nurse-administered telephone follow-up programs have demonstrated clinical and cost efficacy in a variety of health care models. However, their efficacy in movement disorders has not been sufficiently addressed. This observational study fills a knowledge gap by reporting the nature of individuals utilizing a nurse-administered telephone service and the reasons for and the outcomes of calls. METHOD: Consecutive calls received by the clinic for a 12-month duration were recorded. A sample of 312 calls from 132 patient charts was analyzed. Variables for analysis and coding schema were determined a-priori and included demographic information as well as information around the reasons for and outcomes of calls. The narratives of documented calls were reviewed retrospectively and responses coded for analysis by a separate researcher. Data was analyzed using descriptive statistical methods. RESULT: Patients made the majority of calls (49%). 27% of calls related to worsening symptoms and another 35% of calls related to medication issues or renewals. The mean call duration was 15.93 minutes. The majority of calls were received mid-way between clinic visits (M = 89.24 days). The nurse resolved 84% of calls independently. The mean number of calls per patient was 2.93. Issues reported by patients were resolved (approximately 90%) without need for follow-up emergency, family, or subspecialty clinic visits. CONCLUSION: The results underscore the complexity of medical issues in a movement disorders population. The current study provides support for a nurse-administered telephone follow-up program in movement disorders.

Robotics-Based Characterization of Sensorimotor Integration in Parkinson's Disease and the Effect of Medication.

Integration of multi-modal sensory inputs and modulation of motor outputs based on perceptual estimates is called Sensorimotor Integration (SMI). Optimal functioning of SMI is essential for perceiving the environment, modulating the motor outputs, and learning or modifying motor skills to suit the demands of the environment. Growing evidence suggests that patients diagnosed with Parkinson's Disease (PD) may suffer from an impairment in SMI that contributes to perceptual deficits, leading to motor abnormalities. However, the exact nature of the SMI impairment is still unclear. This study uses a robot-assisted assessment tool to quantitatively characterize SMI impairments in PD patients and how they affect voluntary movements. A set of assessment tasks was developed using a robotic manipulandum equipped with a virtual-reality system. The sensory conditions of the virtual environment were varied to facilitate the assessment of SMI. A hundred PD patients (before and after medication) and forty-three control subjects completed the tasks under varying sensory conditions. The kinematic measures obtained from the robotic device were used to evaluate SMI. The findings reveal that across all sensory conditions, PD patients had 36% higher endpoint error, 38% higher direction error in reaching tasks, and 43% higher number of violations in tracing tasks than control subjects due to impairment in integrating sensory inputs. However, they still retained motor learning ability and the ability to modulate motor outputs. The medication worsened the SMI deficits as PD patients, after medication, performed worse than before medication when encountering dynamic sensory environments and exhibited impaired motor learning ability.

Visual velocity perception dysfunction in Parkinson's disease.

OBJECTIVE: Compared with motor deficits, sensory information processing in Parkinson's disease (PD) is relatively unexplored. While there is increasing interest in understanding the sensory manifestations of PD, the extent of sensory abnormality in PD has remained relatively unexplored. Furthermore, most investigations on the sensory aspects of PD involve motor aspects, causing confounding results. As sensory deficits often arise in early PD development stages, they present a potential technological target for diagnosis and disease monitoring that is affordable and accessible. Considering this, the current study's aim is to assess visual spatiotemporal perception independent of goal directed movements in PD by designing and using a scalable computational tool. METHODS: A flexible 2-D virtual reality environment was created to evaluate various cases of visual perception. Using the tool, an experimental task quantifying the visual perception of velocity was tested on 37 individuals with PD and 17 age-matched control participants. RESULTS: PD patients, both ON and OFF PD therapy, displayed perceptual impairments (p = 0.001 and p = 0.008, respectively) at slower tested velocity magnitudes. These impairments were even observed in early stages of PD (p = 0.015). CONCLUSION: Visual velocity perception is impaired in PD patients, which suggests impairments in visual spatiotemporal processing occur in PD and provides a promising modality to be used with disease monitoring software. SIGNIFICANCE: Visual velocity perception shows high sensitivity to PD at all stages of the disease. Dysfunction in visual velocity perception may contribute to observed motor dysfunction in PD.

Abnormal Vision-Based Displacement Perception in Parkinson's Disease.

In this work, we investigate the effect of Parkinson's disease (PD), and common corresponding therapies on vision-based perception of motion, a critical perceptual ability required for performing a wide range of activities of daily livings. While PD has been recognized as mainly a motor disorder, sensory manifestation of PD can also play a major role in the resulting disability. In this paper, for the first time, the effect of disease duration and common therapies on vision-based perception of displacement were investigated. The study is conducted in a movement-independent manner, to reject the shadowing effects and isolate the targeted perceptual disorder to the maximum possible extent. Data was collected using a computerized graphical tool on 37 PD patients [6 early-stage de novo, 25 mid-stage using levodopa therapy, six later-stage using deep brain stimulation (DBS)] and 15 control participants. Besides the absolute measurement of perception through a psychometric analysis on two tested position reference magnitudes, we also investigated the linearity in perception using Weber's fraction. The results showed that individuals with PD displayed significant perceptual impairments compared to controls, though early-stage patients were not impaired. Mid-stage patients displayed impairments at the greater of the two tested reference magnitudes, while late-stage patients were impaired at both reference magnitudes. Levodopa and DBS use did not cause statistically significant differences in absolute displacement perception. The findings suggest abnormal visual processing in PD increasing with disease development, perhaps contributing to sensory-based impairments of PD such as bradykinesia, visuospatial deficits, and abnormal object recognition.

A deep explainable artificial intelligent framework for neurological disorders discrimination.

Pathological hand tremor (PHT) is a common symptom of Parkinson's disease (PD) and essential tremor (ET), which affects manual targeting, motor coordination, and movement kinetics. Effective treatment and management of the symptoms relies on the correct and in-time diagnosis of the affected individuals, where the characteristics of PHT serve as an imperative metric for this purpose. Due to the overlapping features of the corresponding symptoms, however, a high level of expertise and specialized diagnostic methodologies are required to correctly distinguish PD from ET. In this work, we propose the data-driven [Formula: see text] model, which processes the kinematics of the hand in the affected individuals and classifies the patients into PD or ET. [Formula: see text] is trained over 90 hours of hand motion signals consisting of 250 tremor assessments from 81 patients, recorded at the London Movement Disorders Centre, ON, Canada. The [Formula: see text] outperforms its state-of-the-art counterparts achieving exceptional differential diagnosis accuracy of [Formula: see text]. In addition, using the explainability and interpretability measures for machine learning models, clinically viable and statistically significant insights on how the data-driven model discriminates between the two groups of patients are achieved.

Intraoperative Localization of STN During DBS Surgery Using a Data-Driven Model.

A new approach is presented for localizing the Subthalamic Nucleus (STN) during Deep Brain Stimulation (DBS) surgery based on microelectrode recordings (MERs). DBS is an accepted treatment for individuals living with Parkinson's Disease (PD). This surgery involves implantation of a permanent electrode inside the STN to deliver electrical current. Since the STN is a very small region inside the brain, accurate placement of an electrode is a challenging task for the surgical team. Prior to placement of the permanent electrode, microelectrode recordings of brain activity are used intraoperatively to localize the STN. The placement of the electrode and the success of the therapy depend on this location. In this paper, an objective approach is implemented to help the surgical team in localizing the STN. This is achieved by processing the MER signals and extracting features during the surgery to be used in a Machine Learning (ML) algorithm for defining the neurophysiological borders of the STN. For this purpose, a new classification approach is proposed with the goal of detecting both the dorsal and the ventral borders of the STN during the surgical procedure. Results collected from 100 PD patients in this study, show that by calculating and extracting wavelet transformation features from MER signals and using a data-driven computational deep neural network model, it is possible to detect the borders of the STN with an accuracy of 92%. The proposed method can be implemented in real-time during the surgery to model the neurophysiological nonlinearity along the path of the electrode trajectory during insertion.

Assessing the effect of current steering on the total electrical energy delivered and ambulation in Parkinson's disease.

Vertical current steering (vCS) divides current between multiple contacts, which reduces radial spread to fine-tune the electric field shape and improves neuroanatomical targeting. vCS may improve the variable responsiveness of Parkinsonian gait to conventional deep brain stimulation. We hypothesized that vCS elicits greater improvement in ambulation in Parkinson's disease patients compared to conventional, single-contact stimulation. vCS was implemented with divisions of 70%/30% and 50%/50% and compared to single-contact stimulation with four therapeutic window amplitudes in current-controlled systems. Walking at a self-selected pace was evaluated in seven levodopa-responsive patients. Integrative measures of gait and stimulation parameters were assessed with the functional ambulation performance (FAP) score and total electrical energy delivered (TEED), respectively. A two-tailed Wilcoxon matched-pairs signed rank test assessed the effect of each stimulation condition on FAP and TEED and compared regression slopes; further, a two-tailed Spearman test identified correlations. vCS significantly lowered the TEED (P < 0.0001); however, FAP scores were not different between conditions (P = 0.786). Compared to single-contact stimulation, vCS elicited higher FAP scores with lower TEED (P = 0.031). FAP and TEED were positively correlated in vCS (P = 2.000 × 10-5, r = 0.397) and single-contact stimulation (P = 0.034, r = 0.205). Therefore, vCS and single-contact stimulation improved ambulation similarly but vCS reduced the TEED and side-effects at higher amplitudes.

PHTNet: Characterization and Deep Mining of Involuntary Pathological Hand Tremor using Recurrent Neural Network Models.

The global aging phenomenon has increased the number of individuals with age-related neurological movement disorders including Parkinson's Disease (PD) and Essential Tremor (ET). Pathological Hand Tremor (PHT), which is considered among the most common motor symptoms of such disorders, can severely affect patients' independence and quality of life. To develop advanced rehabilitation and assistive technologies, accurate estimation/prediction of nonstationary PHT is critical, however, the required level of accuracy has not yet been achieved. The lack of sizable datasets and generalizable modeling techniques that can fully represent the spectrotemporal characteristics of PHT have been a critical bottleneck in attaining this goal. This paper addresses this unmet need through establishing a deep recurrent model to predict and eliminate the PHT component of hand motion. More specifically, we propose a machine learning-based, assumption-free, and real-time PHT elimination framework, the PHTNet, by incorporating deep bidirectional recurrent neural networks. The PHTNet is developed over a hand motion dataset of 81 ET and PD patients collected systematically in a movement disorders clinic over 3 years. The PHTNet is the first intelligent systems model developed on this scale for PHT elimination that maximizes the resolution of estimation and allows for prediction of future and upcoming sub-movements.

Botulinum toxin in the treatment of lingual movement disorders.

Lingual movement disorders are a rare but serious manifestation of neurologic disease, which have the potential to cause significant morbidity. Traditionally, these disorders were treated with pharmacotherapy achieving only limited results. Several case series have demonstrated the effectiveness of Botulinum toxin injection for the management of focal lingual movement disorders; however, apprehension persists regarding intralingual injections due to the risk of dysphagia. Here, we report seven patients with lingual movement disorders treated with intralingual Botox (Allergan product) injections via a novel superior approach into the genioglossus over a period of 3 to 72 months. All patients experienced a marked improvement in their abnormal tongue movements with no substantial bleeding or dysphagia. Lingual Botulinum toxin injection should be considered a safe and viable treatment option for a variety of disorders affecting the tongue.

A palliative approach to neurological care: a literature review.

This review assesses the current opinion towards early palliative care in neurology and discusses the existing evidence base. A comprehensive literature search resulted in 714 publications with 53 being directly relevant to the scope of this review. The current literature reflects primarily expert opinion and describes a growing interest in the early introduction of palliative principles into neurological care. Early initiation of palliative interventions has the potential to improve quality of life, enhance symptom management and assist in advance care planning. Further data is required to determine whether this shift in philosophy has a positive impact on patient care.

Botulinum toxin A injection into the entopeduncular nucleus improves dynamic locomotory parameters in hemiparkinsonian rats.

Parkinson's disease is associated with hyperactivity of the subthalamic nucleus (STN), contributing to motor and gait disturbances. Although deep brain stimulation of the STN alleviates certain motor dysfunction, its specific effect on gait abnormalities remains controversial. This study investigated the long-term changes in locomotion following direct infusions of botulinum toxin-A into the globus pallidus internal segment (GPi) to suppress the flow of information from the STN to the GPi in a hemiparkinsonian rat model. Static and dynamic gait parameters were quantified using a CatWalk apparatus. Interestingly, botulinum toxin-A at 0.5 ng significantly reduced only the dynamic gait parameters of hemiparkinsonian rats at 1 week and 1 month post-infusion, while static gait parameters did not change. This study offers new insights into the complexity of basal ganglia in locomotor control and shows the potential of central infusion of botulinum toxin-A as a novel intervention in the study of experimental hemiparkinson's disease.

Intrapallidal injection of botulinum toxin A recovers gait deficits in a parkinsonian rodent model.

AIM: Modulation of electrical activity in the subthalamic nucleus has been therapeutically effective in Parkinson's disease. Pharmacological manipulation of glutamate release from subthalamic neurons could also favourably alter basal ganglia activity to improve motor symptoms. This study investigates the efficacy of selective suppression of hyperactive glutamatergic input from the subthalamic nucleus to the globus pallidus internal segment by botulinum toxin A (BoNT-A) in a parkinsonian model. METHODS: Unilateral 6-hydroxydopamine lesioned parkinsonian rodents and controls received microinfusions of BoNT-A or vehicle into the ipsilateral internal globus pallidus (n = 8 per group). Changes in gait were measured by the CatWalk apparatus, along with assessment of apomorphine-induced rotational behaviour prior to and following BoNT-A injection. Immunofluorescent staining for markers of glutamatergic, GABAergic and total terminals was performed at the internal globus pallidus. RESULTS: Administration of a single dose of BoNT-A (0.5 ng) significantly improved the rotational asymmetry and gait abnormalities. Ameliorations in speed, body speed variation, cadence and walking pattern were comparable to pre-lesioned animals, and persisted up to 1 month following BoNT-A injection. These changes are associated to BoNT-A's ability to selectively target glutamatergic terminals. CONCLUSION: Blockade of subthalamic hyperactivity by BoNT-A leads to sufficient reorganization in the basal ganglia needed to generate a consistent rhythmic pattern of walking. This suggests the potential use of intracerebral BoNT-A to produce effective neuromodulation in the parkinsonian brain, as well as expansion into other neurodegenerative disorders linked to excitotoxity.